Methods, systems, and apparatus for modulating circadian cycles

ABSTRACT

An optical filter may reduce the frequency and/or severity of photophobic responses or for modulating circadian cycles by controlling light exposure to cells in the human eye in certain wavelengths, such as 480 nm and 590 nm, and a visual spectral response of the human eye. The optical filter may disrupt the isomerization of melanopsin in the human eye reducing the availability of the active isoform, whereas the attenuation of light weighted across the action potential spectrum of the active isoform attenuates the phototransduction cascade leading to photophobic responses. Embodiments of an optical filter are described. In one embodiment an optical filter may be configured to transmit less than a first amount of light in certain wavelengths, and to transmit more than a second amount of light weighted across the visual spectral response. Methods of use and methods of manufacturing optical filters are also described.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/673,264, filed Aug. 9, 2017, entitled “METHODS, SYSTEMS, ANDAPPARATUS FOR REDUCING THE FREQUENCY AND/OR SEVERITY OF PHOTOPHOBICRESPONSES OR FOR MODULATING CIRCADIAN CYCLES,” which is acontinuation-in-part of U.S. patent application Ser. No. 14/338,182,filed Jul. 22, 2014, entitled “METHODS, SYSTEMS, AND APPARATUS FORREDUCING THE FREQUENCY AND/OR SEVERITY OF PHOTOPHOBIC RESPONSES OR FORMODULATING CIRCADIAN CYCLES,” now U.S. Pat. No. 9,764,157, issued Sep.19, 2017, which is a continuation-in-part of U.S. patent applicationSer. No. 14/160,374, filed Jan. 21, 2014, entitled “METHODS, SYSTEMS,AND APPARATUS FOR REDUCING THE FREQUENCY AND/OR SEVERITY OF PHOTOPHOBICRESPONSES OR FOR MODULATING CIRCADIAN CYCLES”, now U.S. Pat. No.9,759,848, issued Sep. 12, 2017, which is a continuation-in-part of U.S.patent application Ser. No. 13/979,876, filed Feb. 24, 2014, entitled“APPARATUS AND METHODS FOR REDUCING FREQUENCY OR SEVERITY TO PHOTOPHOBICRESPONSES OR MODULATING CIRCADIAN CYCLES”, now U.S. Pat. No. 9,606,277,issued Mar. 28, 2017, which is a national stage application of PCTPatent Application Ser. No. PCT/US2012/021500, filed Jan. 17, 2012,entitled “APPARATUS AND METHODS FOR REDUCING FREQUENCY OR SEVERITY TOPHOTOPHOBIC RESPONSES OR MODULATING CIRCADIAN CYCLES”, which claims thebenefit of and priority to U.S. Provisional Patent Application Ser. No.61/433,344, filed Jan. 17, 2011, entitled “METHODS, SYSTEMS, ANDAPPARATUS FOR REDUCING THE FREQUENCY AND/OR SEVERITY OF PHOTOPHOBICRESPONSES OR FOR MODULATING CIRCADIAN CYCLES”, the disclosures of whichare each incorporated herein by reference in their entireties.

BACKGROUND OF THE DISCLOSURE 1. The Field of the Invention

Photophobia, or light sensitivity, describes an adverse response tolight that characterizes several neurologic conditions. The presentinvention relates to managing the effects of light on a subject. Moreparticularly, the present invention relates to methods, systems, andapparatus for reducing the frequency and/or severity of photophobicresponses or for modulating circadian cycles.

2. The Relevant Technology

The retina of the eye contains various photoreceptor cells. Thesephotoreceptor cells include rods (which are involved in black-and-whiteand low light vision), cones (which are involved in daytime vision andcolor perception), and melanopsin ganglion cells.

The melanopsin ganglion cells are photosensitive. This photosensitivitycan transmit pain through the pain pathways of the brain. These pathwaysare further described by Noseda et al. in A Neural Mechanism forExacerbation of Headache by Light Nat Neurosci. 2010 February;13(2):239-45 PMID 20062053, which is hereby incorporated by reference inits entirety. It has been demonstrated previously that modulatingambient light through the use of spectacle tints can be effective in thetreatment of light-sensitive neurological conditions including migraineand benign essential blepharospasm. A description of these beneficialeffects may be found in Good et al. The Use of Tinted Glasses inChildhood Migraine Headache. 1991 September; 31(8):533-6 PMID 1960058and Blackburn et al. FL-41 Tint Improves Blink Frequency LightSensitivity and Functional Limitations in Patients with Benign EssentialBlepharospasm Ophthalmology. 2009 May; 116(5):997-1001 PMID 19410958,which are both hereby incorporated by reference in their entirety Inaddition to pain pathways, melanopsin ganglion cells also connect to thesuprachiasmatic nucleus, where they participate in entrainment ofcircadian rhythms. These connections are further described by HannibalJ. Roles of PACAP-containing retinal ganglion cells in circadian timing.Int Rev Cytol. 2006; 251:1-39. Review. PubMed PMID: 16939776, which ishereby incorporated by reference in its entirety.

All animals have an intrinsic “clock” that synchronizes them with theearth's light/dark cycle of 24 hours. This clock establishes an internalrhythm of about (“circa”) one day (“dian”). This phenomenon is describedby Czeisler C A, Gooley J J. Sleep and circadian rhythms in humans. ColdSpring Harb Symp Quant Biol. 2007; 72:579-97. Review. PubMed PMID:18419318, which is hereby incorporated by reference in its entirety.However, in order to stay optimally synchronized with the dark/lightcycle, the body's internal clock must be reset each day. Thisentrainment occurs when light in the environment is absorbed by themelanopsin ganglion cells and a signal is transmitted to that part ofthe brain that serves as the body's “master clock”, the suprachiasmaticnucleus, as described in Czeisler C A. The effect of light on the humancircadian pacemaker. Ciba Found Symp. 1995; 183:254-90; discussion290-302. Review. PubMed PMID: 7656689 and Duffy J F, Wright K P Jr.Entrainment of the human circadian system by light. J Biol Rhythms. 2005August; 20(4):326-38. Review. PubMed PMID: 16077152, both of which arehereby incorporated by reference in their entireties.

Rhodopsin is the photosensitive molecule in the rods and cones of theeye. Rhodopsin has two metastable isomers including an active and aninactive state. When exposed to light, the rhodopsin isomerizes to aninactive isoform. The inactive isoform of rhodopsin can be recycled inthe retinoid cycle. During the retinoid cycle, the rhodopsin leaves thephotoreceptor and enters the retinal pigment epithelium. After beingrecycled to an active isoform, the rhodopsin returns to thephotoreceptor. The melanopsin of the melanopsin ganglion cells isbelieved to undergo a similar process as described in Mure L S, Cornut PL, Rieux C, Drouyer E, Denis P, Gronfier C, Cooper H M. Melanopsinbistability: a fly's eye technology in the human retina. PLoS One. 2009Jun. 24; 4(6):e5991. PubMed PMID: 19551136, which is incorporated herebyby reference in its entirety.

Therefore, it would be desirable to manage the effects of light on asubject. More particularly, it would be desirable to provide methods,systems, and apparatus for reducing the frequency and/or severity ofphotophobic responses. It would be also desirable to provide methods,systems, and apparatus for modulating circadian cycles.

BRIEF SUMMARY

As the melanopsin ganglion cells are sensitive to light wavelengths near480 nm and are associated with pain pathways in humans, managing thepainful effects caused by certain types of light would be desirable. Forexample, stimulation of the melanopsin ganglion cells may affect thefrequency and/or severity of photophobic responses, so it may bebeneficial in some circumstances to reduce the direct light stimulationof these cells, or in other circumstances to reduce the amount ofexposure to light not directly associated with the stimulation of thesecells. These photophobic responses include migraine headache, lightsensitivity associated with a concussion or traumatic brain injury,light sensitive epilepsy, and light sensitivity associated with benignessential blepharospasm. The melanopsin ganglion cells are alsoassociated with circadian cycles. Thus, methods, systems, and apparatusfor reducing the frequency and/or severity of photophobic responsesand/or for modulating circadian cycles by controlling light exposure tomelanopsin ganglion cells or other portions of the eye are provided.

An embodiment of an apparatus for reducing the frequency and/or severityof photophobic responses or for modulating circadian cycles isdescribed. The apparatus includes an optical filter configured totransmit less than a first amount of light weighted across theabsorption spectrum of the bistable isoforms of melanopsin, and totransmit more than a second amount of light weighted across the visualspectral response. As examples, the light spectrum associated with theabsorption spectrum of the active isoform of melanopsin is near 480 nmwavelength, and a light spectrum associated with the absorption spectrumof the inactive isoform of melanopsin is near 590 nm wavelength.

In some embodiments, the first amount of light is about 50% of the lightweighted across the absorption spectrum of one or both of the bistableisoforms of melanopsin and the second amount of light is about 75% orgreater of the light weighted across the visual spectral response. Thefirst amount of light, in other embodiments, is about 25% of the lightweighted across the absorption spectrum of one or both of the bistableisoforms of melanopsin and the second amount of light is about 60% orgreater of the light weighted across the visual spectral response. Infurther embodiments, the first amount of light is approximately all ofthe light weighted across the absorption spectrum of one or both of thebistable isoforms of melanopsin. The second amount of light, in stillfurther embodiments, is approximately all of the light outside of theabsorption spectrum of one or both of the bistable isoforms ofmelanopsin and/or weighted across a spectrum that lies outside theabsorption spectrum of one or both of the bistable isoforms ofmelanopsin, weighted across the visual response spectrum. In yet furtherembodiments, a ratio of the attenuation of the first amount of the lightweighted across the absorption spectrum of one or both of the bistableisoforms of melanopsin to the attenuation of the second amount of thelight weighted across the visual spectral response is more than one.

The first amount of light, in some embodiments, is substantially alllight below a long pass filter wavelength within the action potentialspectrum of the melanopsin ganglion cells and the second amount of lightis all light across the visual spectral response with a wavelength abovethe long pass filter wavelength. In further embodiments, the firstamount of light is substantially all light above a short pass filterwavelength near 590 nm and the second amount of light may besubstantially all light across the visual spectral response with awavelength below the short pass filter wavelength.

In some embodiments, the second amount of light includes a third amountof light having a wavelength that is less than a maximum relativeresponse of the action potential spectrum of the melanopsin ganglioncells and/or greater than about 590 nm. The second amount of light, inother embodiments, includes a third amount of light having a wavelengththat is greater than a maximum relative response of the absorptionspectrum of one or both of the bistable isoforms of melanopsin. Infurther embodiments, the second amount of light includes a third amountof light having a wavelength that is lower than a maximum relativeresponse of the absorption spectrum of one or both of the bistableisoforms of melanopsin and a fourth amount of light that is greater thanthe maximum relative response of the absorption spectrum of one or bothof the bistable isoforms of melanopsin.

In some embodiments, the first amount of light is a dose of light (i.e.across the absorption spectrum of one or both of the bistable isoformsof melanopsin) experienced by a cell in the eye—retinal ganglion cellsor other cells of a subject (D_(rec))—and the second amount of light isa dose of light experienced over the visual response spectrum (D_(vis)),and wherein a ratio including the first amount of light and the secondamount of light is defined as a figure of merit (FOM), the figure ofmerit being determined by:

${FOM} = \frac{1 - \frac{D_{rec}}{D_{rec}\left( {T = 1} \right)}}{1 - \frac{D_{vis}}{D_{vis}\left( {T = 1} \right)}}$

where D_(rec)(T=1) is the first amount of light in the absence of anoptical filter, and D_(vis)(T=1) is the second amount of light in theabsence of an optical filter. The figure of merit of the optical filter,in some embodiments, may include about one, more than about one, morethan about 1.3, more than about 1.5, more than about 1.8, more thanabout 2.75, more than about 3, more than about 3.3. Other figures ofmerit may be used in other embodiments.

In some embodiments, the first amount of light defines a spectral widththat has a median at a median of the absorption spectrum of one or bothof the bistable isoforms of melanopsin. The first amount of light andthe second amount of light, in further embodiments, are determined basedon the characteristics of ambient light. In still further embodiments,the first amount of light and the second amount of light are selectivelyadjustable by way of a transition, -photochromic, or electrochromic typedye, pigment or coating.

The optical filter, in some embodiments, includes at least one layerconfigured to minimize or reduce the effect of an angle of incidence ofthe received light. In further embodiments, the optical filter furthercomprises a substrate that includes a tint by impregnation or bycoating.

An embodiment of a system for reducing the frequency and/or severity ofphotophobic responses or for modulating circadian cycles is described.The system includes a substrate, a first layer disposed on thesubstrate, and a second layer disposed adjacent the first layer. Thefirst layer includes a high index material. The second layer includes alow index material.

In further embodiments, the system may include additional layers and/ortypes of material, wherein the materials cooperate to transmit less thana first amount of light weighted across the action potential spectrum ofthe melanopsin ganglion cells and to transmit more than a second amountof light weighted across the visual spectral response. In someembodiments, increasing the number of layers in the optical filterincreases transmission of light outside the action potential spectrum.

An embodiment of a method of manufacturing an optical filter forreducing the frequency and/or severity of photophobic responses isdescribed. The method includes determining an appropriate lightspectrum. A first light dose to be experienced by one or both of thebistable isoforms of melanopsin in the subject is determined. A secondlight dose associated with the visual response spectrum is determined.An optical filter is manufactured using the first light dose and thesecond light dose.

In some embodiments, an action potential spectrum of an individual'smelanopsin ganglion cells is determined. The optical filter, in furtherembodiments, is configured to attenuate the first amount of light basedon the individual's melanopsin ganglion cells. In still furtherembodiments, the optical filter is manufactured based on visual responsespectrum characteristics.

The optical filter, in some embodiments, is a notch filter. In furtherembodiments, the notch filter is configured to block light that strikesat a non-normal incidence angle. The notch filter, in still furtherembodiments, includes a filter optimized for a plurality of tiltedincidence angles. In yet further embodiments, the notch filter isdesigned with a slight red shift. The notch filter, in even furtherembodiments, includes a filter notch that attenuates light across aspectral width.

In some embodiments, manufacturing of the optical filter includes usingdielectric multi-layers, embedded nanoparticle coatings, a color filter,tint, resonant guided-mode filter, a rugate filter, and any combinationthereof. The embedded nanoparticle coatings, in further embodiments,include at least one of metallic nanoparticles, dielectricnanoparticles, semiconductor nanoparticles, quantum dots, magneticnanoparticles, or core-shell particles having a core material in a coreand a shell material serving as a shell. In still further embodiments,the at least metallic nanoparticles include at least one of Al, Ag, Au,Cu, Ni, Pt, or other metallic nanoparticles, wherein the dielectricnanoparticles include at least one of TiO₂, Ta₂O₅, or other dielectricnanoparticles. The semiconductor nanoparticles or quantum dots, in yetfurther embodiments, include at least one of Si, GaAs, GaN, CdSe, CdS,or other semiconductor nanoparticles. In even further embodiments, ashape of the embedded nanoparticles in the embedded nanoparticlecoatings is spherical, elliptical, or otherwise shaped. In someembodiments, an extinction spectrum of the embedded nanoparticles isdetermined using Mie scattering theory.

An embodiment of a method for reducing the frequency and/or severity ofphotophobic responses or for modulating circadian cycles is described.The method includes receiving an amount of light. Less than a firstamount of the light weighted across the absorption spectrum of one orboth of the bistable isoforms of melanopsin is transmitted. More than asecond amount of the light weighted across the visual spectral responseis transmitted. The attenuation of light weighted across the absorptionspectrum of one or both of the bistable isoforms of melanopsin disruptsthe isomerization of one or both of the bistable isoforms of melanopsin.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings constitute a part of this specification and includeexemplary embodiments of the invention, which may be embodied in variousforms. It is to be understood that in some instances various aspects ofthe invention may be shown exaggerated or enlarged to facilitate anunderstanding of the invention.

FIG. 1 illustrates an exemplary measured action potential spectrum formelanopsin cells, which is normalized to unity magnitude, with aGaussian fit to the measured data points.

FIG. 2 illustrates the measured transmission spectrum of an exemplary“FL-41 35” filter across the “effective action potential spectrum” ofmelanopsin.

FIG. 3 illustrates the measured transmission spectrum of an exemplary“FL-41 35” filter across the visible light spectrum.

FIG. 4 illustrates the measured transmission spectrum of an exemplary“FL-41 55” filter across the “effective action potential spectrum” ofmelanopsin.

FIG. 5 illustrates the measured transmission spectrum of an exemplary“FL-41 55” filter across the visible light spectrum.

FIG. 6 is an example of a filter using multi-layer dielectric thin filmsof distinct refractive indices.

FIG. 7 is an example of a filter using an embedded nanoparticle coatingdesigned to scatter light in the aqua region of the visible lightspectrum.

FIG. 8 illustrates an exemplary method for designing an optical filterto block light absorption by melanopsin cells

FIG. 9 illustrates the measured transmission spectrum of one embodimentof a filter across the “effective action potential spectrum” ofmelanopsin.

FIG. 10 illustrates the measured transmission spectrum of the embodimentof a filter in FIG. 9 across the visible light spectrum.

FIG. 11 illustrates the measured transmission spectrum of anotherembodiment of a filter across the “effective action potential spectrum”of melanopsin.

FIG. 12 illustrates the measured transmission spectrum of a furtherembodiment of a filter across the “effective action potential spectrum”of melanopsin.

FIG. 13 illustrates the measured transmission spectrum of a stillfurther embodiment of a filter across the “effective action potentialspectrum” of melanopsin.

FIG. 14 illustrates the measured transmission spectrum of the embodimentof a filter in FIG. 13 across the visible light spectrum.

FIG. 15 illustrates the measured transmission spectrum of an evenfurther embodiment of a filter with the center of the filter positionedat 485 nm for normal light incidence across the “effective actionpotential spectrum” of melanopsin.

FIG. 16 illustrates the measured transmission spectrum of the embodimentin FIG. 15 with an incidence angle of 15 degrees across the “effectiveaction potential spectrum” of melanopsin.

FIG. 17 illustrates the measured transmission spectrum of a yet furtherembodiment of a filter excluding a low-index MgF₂ layer across the“effective action potential spectrum” of melanopsin.

FIGS. 18A and B illustrate the measured transmission spectrum of anembodiment of a filter centered at about 480 nm and an embodiment of afilter centered at about 620 nm.

FIG. 19 illustrates the measured transmission spectrum of multipleembodiments of filters centered at about 480 nm with varying degrees oftint.

FIG. 20 illustrates the backside reflection spectra of the embodimentsof filters in FIG. 19.

FIG. 21 illustrates an exemplary embodiment of a method of manufacturingan optical filter.

FIG. 22 illustrates an exemplary embodiment of a method for reducing thefrequency and/or severity of photophobic responses or for modulatingcircadian cycles.

FIG. 23 illustrates an embodiment of a composite filter configured topreferentially attenuate two ranges of wavelengths.

FIG. 24 illustrates an embodiment of a method of manufacturing acomposite optical filter.

FIG. 25 illustrates an embodiment of a method using a composite filterfor reducing the frequency and/or severity of photophobic responses orfor modulating circadian cycles.

FIGS. 26A and B illustrate the transmission spectra of gray tintedlenses coatings centered at 480 nm and 620 nm, respectively.

FIG. 27 schematically illustrates the cyclic isomerization of a bistablepigment.

FIG. 28 illustrates the reactive spectra of active and inactivemelanopsin in the eye.

FIG. 29 illustrates an embodiment of a method of disrupting theisomerization of one or both of the bistable isoforms of melanopsin.

FIG. 30 illustrates the relative response versus the wavelength of lightaccording to sample color-matching functions.

FIG. 31 illustrates the relative response versus the wavelength of lightaccording to sample color-matching functions when a 480 nm filter isused.

FIG. 32 illustrates the relative response versus the wavelength of lightaccording to sample color-matching functions when both a 480 nm filterand a 590 nm filter are used.

DETAILED DESCRIPTION

Detailed descriptions of embodiments of the invention are providedherein. It is to be understood, however, that the present invention maybe embodied in various forms. Therefore, the specific details disclosedherein are not to be interpreted as limiting, but rather as arepresentative basis for teaching one skilled in the art how to employthe present invention in virtually any detailed system, structure, ormanner.

The present invention relates to managing the effects of light on asubject. Some applications of the present invention relate to methods,systems, and apparatus for reducing the frequency and/or severity ofphotophobic responses or for modulating circadian cycles.

Different individuals experience photophobic responses in differentways. The wavelengths and, therefore, pathways that trigger adversereactions to light can vary depending on the patient. However, there aresome common wavelengths that are more commonly associated withphotophobic responses than others. For example, the melanopsin ganglioncells in the eye are sensitive to light at a wavelength of about 480 nm.In some individuals, this may be linked to those individual'slight-sensitive neurological conditions. Controlling exposure to lightnear the 480 nm wavelength may yield benefits to those individuals andreduce or prevent their light-sensitive neurological conditions.Alternatively or in addition, regulating exposure to that same light mayalso assist in controlling an individual's circadian rhythms. In thesame or other individuals, regulating the exposure of the eye to lightnear a 620 nm wavelength or other wavelengths may also yield benefits inreducing or preventing light-sensitive neurological conditions ormanaging an individual's circadian rhythms. While the following examplerefers to the attenuation of light having wavelengths near 480 nm andthe exposure of melanopsin ganglion cells to the same light near 480 nm,it may be understood that a similar filter and methods may be used toattenuate light at other wavelengths and received by other cells in theeye. For example, a similar filter and method may be used to attenuatelight at or about 620 nm. In another example, a similar filter andmethod may be used to attenuate light at or about 590 nm.

Because the melanopsin ganglion cells have been implicated inphotophobia and in the onset of migraines in a number of photophobicsubjects, it is desirable to block at least portions of that part of thevisible spectrum that activates these cells. Photophobia is associatedwith light-sensitive neurological conditions, including migraineheadaches, benign essential blepharospasm and traumatic brain injury(TBI). FIG. 1 illustrates an example of the measured action potentialspectrum for melanopsin cells, which is normalized to unity magnitude,and a Gaussian fit to the measured data points. This Gaussian fit may beused in at least one embodiment of a filter design, but this should notbe interpreted as the spectral basis for optimal filters, as morerefined measurements of the action potential spectrum may becomeavailable. These refined measurements may motivate additional filterdesigns or methods following the process described here, or via similarprocesses. Optimizations of the methods, systems, and apparatusdescribed herein based on more refined measurements of the actionpotential spectrum are contemplated.

In some embodiments, light may be blocked (i.e. attenuated) over acertain wavelength range appropriate for photophobia prevention, whileminimizing the distortion of the visible spectrum. In other embodiments,the methods, systems, and apparatus described in this application mayalso be used to manipulate the body's circadian system.

Embodiments of optical filters are described that block a certain partof the optical spectrum that is suspected to trigger and/or exacerbatethese photophobic responses. These filters can be applied to eyewear(such as spectacles, goggles, clip-ons, or other eyewear), lenses(including contact lenses), computer screens, windows, car windshields,lighting substrates, light bulbs (incandescent, fluorescent, CFL, LED,gas vapor, etc.), or any other optical element. These optical filtersmay be applied to crown glasses (including BK7), flint glasses(including BaF₈), SiO₂, plastics (such as polycarbonate, CR-39, andtrivex), other substrates, and combinations thereof.

Although the majority of the description focuses on photophobiaprevention, the systems, methods, and apparatus described herein arealso applicable to modulating circadian rhythm. For example, thesefilters could be used for manipulation of the body's circadian system bybusiness people, athletes, others who travel between different timezones, or those who desire to manipulate the body's circadian system. Inone example, a subject would wear at least one of the filters describedherein to help them adapt to the light/dark cycle of the locale to whichthey are traveling. In another example at least one of the filtersdescribed herein could also be used to limit excitation of themelanopsin ganglion cells in patients with sleep disorders. In this use,a subject could wear these filters to limit their exposure to artificiallight in the evening, and prevent their internal clocks from thinkingthat it is time to stay awake. In addition, subjects may increaseexposure to light before sunrise to adjust their light/dark cycle.

Furthermore, it has also been recently clinically demonstrated thatwavelengths near 620 nm also contribute to photophobic effects incertain individuals. While the precise pathways for the neurologicaleffects are not currently fully understood, benefits may be achieved bypreferentially attenuating light with wavelengths near 620 nm, as well.

Melanopsin has bistable isoforms that each exhibit unique absorptionspectra. The isoforms may be an active isoform and an inactive isoform.The active isoform may be physiologically active. The inactive isoformmay be physiologically inactive. Absorption of light in accordance witheach isoform's absorption spectrum may lead to the isomerization of themelanopsin. Benefits may be achieved by disrupting, limiting, orpreventing the isomerization of melanopsin by attenuating light at orabout 590 nm.

The FL-41 lens tint is sometimes prescribed for migraine patients. TheFL-41 tint blocks (via absorption) a broad range of wavelengths. Thesewavelengths include wavelengths associated with melanopsin absorption.The FL-41 dye can be infiltrated into certain types of plastic spectaclelenses. The amount of dye infiltrated generally determines the amount oflight intensity blocked. The “FL-41 35” tinting is effective for anumber of patients in indoor environments. However, if the light sourceincreases in intensity, by for example moving to an outdoor environment,the “FL-41 35” may not be as effective.

FIG. 2 shows the measured transmission spectrum of “FL-41 35”. FIG. 2also illustrates the effect of the “FL-41 35” filter on the actionpotential spectrum of melanopsin, a so-called “effective actionpotential spectrum.” The “FL-41 35” tinting blocks, or attenuates, about55% of the light that would otherwise be absorbed by the melanopsinganglion cells. The FL-41 tinting further blocks a significant portionof the visible spectrum that is not associated with melanopsin, as shownin FIG. 3, with about a 47% attenuation across the visual responsespectrum. The additional blocking the visible response spectrum may bedisadvantageous. For example, blocking the visible response spectrum mayadversely affect normal vision. In another example, blocking the visibleresponse spectrum may produce a false coloration that may be distractiveor otherwise less desirable for the wearer.

For bright light situations, such as outdoor environments, a tintingwith greater level of spectral attenuation may be used, such as “FL-4155.” The transmission spectrum of this filter, along with its effect onthe action potential spectrum, is shown in FIGS. 4 (across the“effective action potential spectrum” of melanopsin) and 5 (across thevisible light spectrum). This filter attenuates about 89% of the lightthat would otherwise be absorbed by melanopsin cells, but alsoattenuates about 81% of the visual response spectrum. This additionalspectral attenuation can also impair vision in low light levels or othersituations.

Overall, the general drawbacks to FL-41 include: a rose coloredappearance, distorted color perception; limited applicability (i.e. itmay only be applied to certain plastics and may not be applied to glasslenses, computer screens, windows, car windshields, lighting substrates,light bulbs, or other optical elements); and poor quality control overthe tinting process (due in part to variations in the tintable hardcoating layers). Although FL-41 may be effective in certainapplications, it is not designed to down-regulate the stimulation of themelanopsin ganglion cells and their connections to pain centers in thebrain. For these reasons, it may be desirable to develop otherembodiments of filters.

One example of a more desirable optical filter for the treatment oflight sensitive conditions may include a long-pass filter. To regulateexposure of the melanopsin ganglion cells to wavelengths of about 480nm, a long pass filter may highly transmit wavelengths longer than about500 nm or 520 nm, while attenuating light at wavelengths shorter thanabout 500 nm or 520 nm. Similarly, to regulate exposure of cells in thehuman eye to wavelengths of about 620 nm, a short pass filter may highlytransmit wavelengths shorter than 600 nm or about 580 nm, whileattenuating light at wavelengths longer than about 600 nm or about 580nm.

Other examples of more desirable optical filters may include filtersthat only block the spectrum of light absorbed by melanopsin or otherspecific wavelengths, while generally transmitting the rest of the lightspectrum, with the spectral transmission response of the filter takingthe form of a notch, sometimes called a band stop or minus filter. Inthe case of melanopsin the center position of the notch may be near theabsorption maximum of the melanopsin pathway (about 480 nm), but otherpositions may be effective. The spectral width of the notch mayapproximately match the width of the action potential spectrum, which isabout 50 to 60 nm, although other widths are contemplated.

Optical filter technologies such as tints comprised of dye mixtures,dielectric multi-layers (an example of which is shown in FIG. 6), andembedded nanoparticle coatings (an example of which is shown in FIG. 7),other filter technologies such as resonant waveguide filters, orcombinations thereof may be used to create a filter according to thepresent disclosure. Nanoparticle coatings that may be used for opticalfilters according to the present disclosure may include metallicnanoparticles (e.g. Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles(e.g. TiO₂, Ta₂O₅, etc.), semiconductor nanoparticles or quantum dots(e.g. Si, GaAs, GaN, CdSe, CdS, etc.), magnetic nanoparticles,core-shell particles consisting of one material in the core and anotherserving as a shell, other nanoparticles, or combinations thereof. Shapesof these particles may be spherical, ellipsoidal, otherwise shaped, orcombinations thereof. Host materials may include polymers, sol-gels,other host materials, or combinations thereof. The extinction spectrumof these nanoparticles can be calculated using Mie scattering theory orvariations thereof.

An embodiment of a multi-layer filter 600, shown in FIG. 6, includes asubstrate 602, a first layer 604, and a second layer 606. As shown, thefirst layer 604 may include a high index material and the second layer606 may include a low index material. In other embodiments, the firstlayer 604 may include a low index material and the second layer mayinclude a high index material. Additionally, the first layer 604 isshown adjacent the substrate 602. In other embodiments, the first layer604 may have another layer (for example, second layer 606 and/or anotherlayer) between the substrate 602 and the first layer 604. Additionallayers are also shown (though not numbered). The substrate 602 mayutilize any substrate described herein. For example, the substrate 602may include a tinted layer (not shown) on the same and/or opposite sideof the first layer 604 and second layer 606 (i.e. the front and/or backside of the substrate). In another example, the substrate 602 itself maybe impregnated with tint. Examples of tinting techniques and amounts aredescribed below. Other embodiments of multi-layer filters are furtherdescribed herein.

A filter 700, shown in FIG. 7, includes a substrate 702, a host layer704, and a plurality of nanoparticles 706. The host layer 704 is shownadjacent the substrate 702. In other embodiments, the host layer 704 mayhave another layer (for example, second layer 606 from FIG. 6 and/oranother layer) between the substrate 702 and the host layer 704.Although the nanoparticles 706 are shown as spherical and uniformlysized, as described above, other shapes and sizes are contemplated. Aswith the multi-layer filter of FIG. 6, various substrates, tints, otherfeatures, or combinations thereof may be used with the nanoparticlefilter 700. Other embodiments of nanoparticle filters are describedherein.

Other types of filters that may be used may include color filters(organic dye and semiconductor), resonant guided-mode filters, rugatefilters, or combinations thereof. A rugate filter utilizes a sinusoidalrefractive index variation throughout its thickness. A true sinusoid maynot be obtainable and is often approximated by a staircase refractiveindex approximation using the mixture of two or more materials.

In addition to these various filter types, further considerations maytake into account the effect of the designed filter on the visualresponse spectrum, as determined by the photoresponse of the rods andcones. One consideration may include minimizing spectral distortion.Adding additional or other constraints on filter design may beconsidered, including optimization methods, such as taking angularsensitivity into account, which can be compensated for, using dielectricmulti-layers, for example, when attenuating light near 480 nmapproaching melanopsin ganglion cells, by designing the center of thenotch to be slightly red-shifted from about 480 nm to account for theblue-shift of the filter response that occurs for off-axis illumination.Depending on the wavelength attenuated, the degree of red-shift orblue-shift may vary. Optimization may further include widening thefilter spectral width to compensate for non-normal incidence angles,and/or through the use of additional filter layers to compensate forangle of incidence. The potential for backside reflection may be aconsideration. One or more of these considerations may be addressed bycombining the filter with some form of tinting.

One embodiment of a method for manufacturing an optical filter to blocklight absorption by melanopsin cells is described herewith. The lightdose D experienced by melanopsin cells can be written

$\begin{matrix}{D_{melan} = {\int{{L(\lambda)}{T(\lambda)}{M(\lambda)}\ d\;\lambda}}} & (1)\end{matrix}$where L is the light spectrum (in terms of intensity, power,photons/sec, etc.), T is the spectral transmission of a filter lyingbetween the light source and the eye, and M is the normalized actionpotential response spectrum of melanopsin, as currently estimated fromFIG. 1 as a Gaussian function centered at 480 nm with a full-width athalf-maximum of 52 nm. For generality, it is assumed that L=1 so as notto limit discussion to any specific light source, however analyses maybe performed for any light source of known spectrum.

A similar dose can be calculated in association with the visual responsespectrum

$\begin{matrix}{D_{vis} = {\int{{L(\lambda)}{T(\lambda)}{V(\lambda)}d\;\lambda}}} & (2)\end{matrix}$where V represents the normalized visual response spectrum.

The effect of an optical filter, such as the FL-41 tint, is to reducethe dose, as described by taking the ratio of dose calculated with thefilter to dose without the filter, for example

$N_{melan} = \frac{D_{melan}}{D_{melan}\left( {T = 1} \right)}$

The “attenuation” of the dose may be written as, for example,

$A_{melan} = {{1 - N_{melan}} = {1 - \frac{D_{melan}}{D_{melan}\left( {T = 1} \right)}}}$

A figure of merit (FOM) can also be defined which compares the blockingof the melanopsin response to the blocking of the visual responsespectrum

$\begin{matrix}{{FOM} = \frac{1 - \frac{D_{melan}}{D_{melan}\left( {T = 1} \right)}}{1 - \frac{D_{vis}}{D_{vis}\left( {T = 1} \right)}}} & (3)\end{matrix}$which represents the ratio of the attenuation of light across themelanopsin spectrum to the attenuation of light across the visiblespectrum, where a value of FOM>1 may be desirable. For the FL-41 tint,FOM is about 1.

FIG. 8 illustrates one embodiment of a method 800 for designing anoptical filter to block light absorption by melanopsin cells that mayinclude determining the light dose D experienced by melanopsin cells(using, for example, Equation 1), as illustrated by act 802. The lightdose experienced across the visual response spectrum may be determined(using, for example, Equation 2), as illustrated by act 804. A figure ofmerit (FOM) may be determined with respect to the light dose experiencedby the melanopsin cells and to the light dose experienced across thevisual response spectrum, as illustrated by act 806. In otherembodiments, the dose across the visual response spectrum may be reducedor separated. For example, only a portion or portions of the visualresponse spectrum may be used, or wavelengths outside the visualresponse spectrum may be considered. The figure of merit may be used todesign an optical element to reduce and/or prevent photophobicresponses.

Many embodiments described herein use multi-layer dielectric thin filmsof distinct refractive indices. These layers may be applied to a numberof optical elements (as described herein). By way of example, and in noway intended to be limiting, embodiments of optical filter designs ofthe present disclosure assume a generic transparent substrate, such as aspectacle lens, with refractive index around 1.5, and with ananti-reflection coating applied to the back surface (i.e. the surfaceclosest to the user's eye). Thus, other substrates with other refractiveindices, and with or without back surface anti-refection coatings, arecontemplated. Minor variations in filter design may be required tocompensate for different substrate materials and/or different coatingson those substrates. Further considerations may need to be addressedsuch as compatibility of different thin-film materials with differentsubstrate materials, which may require further design optimization, andthe curvatures of the lens substrate. The substrate may include anadhesion layer (for example a thin layer of chromium) between thesubstrate, or a layer on the substrate, and any further coatings.

There are a multitude of design approaches to multi-layer long-pass andnotch filters which may be used. For example, software and other designtools are available for the design of thin film optical filters. Thesetools may take a number of constraints into account during optimization,reducing the likelihood that any two filter designs will be identical,even if accomplishing the same light blocking characteristics orproducing the same physiological result. Only a few examples will bepresented here and are not meant to be limiting in any way. Otherapproaches could be taken to achieve similar results, and furtheroptimizations could be performed in order to produce more idealcharacteristics, or to produce similar characteristics with fewer numberof layers, in accordance with the present disclosure.

In addition, multi-layer and other coatings may be applied to tintedlenses or substrates. There are multiple reasons why this combinationmay be desirable. One reason may include that the spectralcharacteristics of the tint may relax design constraints on the thinfilm filter. For example, combining an FL-41 “base tint” with athin-film notch filter may serve to reduce the depth of the notchnecessary to produce a therapeutic outcome. It may be desirable to takeinto account the spectral variation of transmission of the tint in thenotch design. This design adjustment may be accomplished by, forexample, shifting the center wavelength of the notch to compensate forthe local slope of the tint spectral response. Another reason for usinga base tint may be to reduce any undesirable reflection of light thatenters though the backside of the lens. In this situation, it may bedesirable to use a “flat,” or neutral density, tint that would notintroduce any coloration in and of itself.

For example, in an embodiment of a filter designed to block a range ofwavelengths of light from passing through the front of the lens (by, forexample, reflecting the desired wavelengths away from the user), thelight entering the back side of the lens (which includes light in thewavelengths to be blocked) may be reflected back into the user's eye. Inother words, the light to be blocked from the front (by reflection inthe case of a multi-layer filter) may then be reflected from the back.This may not be a concern in situations where there is a single lightsource that is mainly in front of the subject. However, in situations,for example, where very bright light is found or where there aremultiple light sources, this back reflection may be deleterious to theuser.

One example approach to producing long pass or notch filters includesusing alternating layers of high and low refractive index materials.Example low index dielectric materials include MgF₂ and SiO₂. MgF₂ iscommonly used in single and multi-layer anti-reflection coatings.Example high index materials include metal oxides such as TiO₂, Ti₃O₅,ZrO₂, and Ta₂O₅, and Si₃N₄. Numerous other suitable materials can beused, including polymer layers.

Optical filters for attenuating light near various wavelengths, such as480 nm, 620 nm, or other specific wavelengths, may follow similardesigns. One embodiment of an optical filter design is shown in FIGS. 9and 10, along with the effect of this embodiment of a filter on thespectrum of light that strikes melanopsin cells, producing an effective(and attenuated) action potential. This design is intended to be asclinically effective as the FL-41 35 coating, in that 55% of the lightthat would be absorbed by melanopsin cells is blocked, or attenuated,which should result in the same alleviation of migraine (or lightsensitive) symptoms as the FL-41 coating, but with significantly lessvisual distortion, with only 18% attenuation across the visual response.For this embodiment, the low index material is SiO₂ and the high indexmaterial TiO₂, and MgF₂ is used as the outermost layer, and 11 totallayers are used. Exemplary layers and materials are listed in the tablebelow from the outermost layer (MgF₂) to the innermost layer (TiO₂ with165 nm thickness) adjacent to the substrate. This filter has FOM≈3.

Material Thickness (nm) MgF₂ 126 SiO₂ 212 TiO₂ 125 SiO₂ 134 TiO₂ 129SiO₂ 62 TiO₂ 12 SiO₂ 51 TiO₂ 26 SiO₂ 40 TiO₂ 165

The spectral position of the center of a notch filter may be determinedby the thicknesses of its respective layers. Although many embodimentsherein assume the spectral position of the notch is at about 480 nm,other spectral positions are contemplated. For example, as moreinformation about the action potential spectrum of the melanopsinpathway is known, the spectral position may be shifted in accordancewith the new information, such as to 620 nm. In another example, thespectral position may be otherwise positioned to achieve specificresults, such as to attenuate wavelengths other than those of the actionpotential spectrum of the melanopsin pathway.

The width of the notch may be determined by the difference in refractiveindices of the different layers. The depth of the notch may bedetermined by the number of layers. The transmission outside of thenotch region may be increased and flattened through the inclusion ofadditional layers, and with the possible inclusion of a single ormulti-layer anti-reflection coating applied to the back surface of thelens to reduce backside reflection. Further design optimization can beused to increase the depth of the notch which may further suppressexcitation of melanopsin cells, but the effect on the visual responsespectrum should be considered. Overall suppression may be tailored on apatient-by-patient basis or by designing one or more general classes offilters in order to help the majority of cases.

Greater attenuation of the effective melanopsin action potentialspectrum may be obtained by either deepening or widening the filternotch, or through a combination of both. FIGS. 11 and 12 illustrateembodiments of two exemplary approaches, using 19 and 15 dielectriclayers, respectively. The ultimate choice between the two can be madebased upon wearer preference, as both produce about a 70% attenuationacross the melanopsin spectrum, but have slightly different visualresponse spectrum characteristics. The 19 layer filter attenuates about21% of the visual response spectrum, and the 15 layer filter attenuatesabout 25% of the visual response spectrum. Both filters have FOM valuesgreater than 2.75, with the 19 layer filter having an FOM value of about3.3.

Different designs may achieve significant attenuation across themelanopsin action potential spectrum. FIGS. 13 and 14 show an embodimentof a notch filter design that produces a melanopsin action potentialattenuation similar to the FL-41 55 filter, blocking about 89% of thelight, using 19 dielectric layers, but blocking only about 29% of thevisual response spectrum, with an FOM value of about 3. Exemplary layersand materials are listed in the table below from the outermost layer(MgF₂) to the innermost layer (TiO₂ with 160.3 nm thickness) adjacent tothe substrate.

Material Thickness (nm) MgF₂ 179.9 SiO₂ 152.3 TiO₂ 75.8 SiO₂ 16.9 TiO₂80.5 SiO₂ 35.1 TiO₂ 38.0 SiO₂ 128.6 TiO₂ 66.5 SiO₂ 17.7 TiO₂ 55.5 SiO₂67.5 TiO₂ 88.3 SiO₂ 22.0 TiO₂ 63.1 SiO₂ 30.7 TiO₂ 84.2 SiO₂ 34.8 TiO₂160.3

Other design considerations may include blocking for light that strikesat non-normal incidence angles. For instance, tilting the angle of athin film filter tends to produce a blue-shift in the filter response.This may be accommodated, for example, by either purposefully designingthe filter with a slight red shift, by broadening the width of thefilter, adding additional layers, or combinations thereof to minimize orreduce the effect of the angle of incidence.

FIG. 15 shows an embodiment of a filter design with 10 layers, where thecenter of the notch is positioned at 485 nm for normal light incidence.At normal incidence, this embodiment of a filter blocks about 61% of thelight dose to the melanopsin spectrum and only attenuates about 21% ofthe light to the visual response spectrum, resulting in an FOM value ofabout 2.9.

FIG. 16 shows the effect of the embodiment of a filter from FIG. 15, butwith an incidence angle of about 15 degrees. In this embodiment and atthis incidence angle, blocking of the melanopsin light dose is about 61%with about 20% blocking of the visual response spectrum, resulting in anFOM value of about 3.1.

This embodiment of a filter has the following layer properties listed inthe table below from the outermost layer (MgF₂) to the innermost layer(TiO₂ with 127 nm thickness).

Material Thickness (nm) MgF₂ 117 TiO₂ 88 SiO₂ 190 TiO₂ 78 SiO₂ 192 TiO₂90 SiO₂ 37 TiO₂ 140 SiO₂ 134 TiO₂ 127

In the embodiments of filters described in connection with FIGS. 8-15, alow-index MgF₂ layer was used. Other embodiments may not require thismaterial. For example, FIG. 17 illustrates an embodiment of filterdesign which blocks about 73% of the melanopsin action potentialspectrum (or light dose) and about 21% of the dose of the visibleresponse, with an FOM value of about 3.5. The layer properties of thefilter design illustrated in FIG. 17 are listed in the table below fromthe outermost layer to the innermost layer.

Material Thickness (nm) SiO₂ 58.6 TiO₂ 117.0 SiO₂ 138.0 TiO₂ 57.4 SiO₂18.8 TiO₂ 41.9 SiO₂ 128.5 TiO₂ 149.9 SiO₂ 52.1 TiO₂ 161.1 SiO₂ 187.7TiO₂ 5.4 SiO₂ 45.9 TiO₂ 264.9 SiO₂ 33.1 TiO₂ 9.9 SiO₂ 208.5

As discussed above, it may be desirable to reduce the amount of lightthat is reflected from the back side (i.e. the side closest to theuser's eye) into the user's eye. This may be accomplished by anotherembodiment of a filter design in which a thin film coating may beapplied onto a tinted lens or substrate. In other embodiments, thesubstrate may be tinted by impregnation, coating, other tintingtechniques, or combinations thereof. The transmission of light through athin-film coating/tinted substrate combination may be written as theproduct of the transmission of the thin-film coating and thetransmission of the tinted substrate:T(λ)=T _(film)(λ)T _(tint)(λ)  (4)assuming that the thin-film coating is applied only to the front surfaceof the substrate and assuming that an anti-reflection coating (with T≈1)is applied to the back surface of the substrate.

For light entering the back surface of the substrate, it first passesthrough the tint, is reflected from the thin-film filter on the frontsurface of the substrate, then passes through the tint a second timebefore striking the user's eyes. For this situation, the reflected lightmay be writtenR(λ)=T _(tint)(λ)[1−T _(film)(λ)]T _(tint)(λ)=R _(film)(λ)T _(tint)²(λ)=T _(tint)(λ)[T _(tint)(λ)−T(λ)]  (5)

At any particular wavelength, the fraction of light transmitted andreflected may be set by the transmission of the thin film coating andtint. For example, if about 20% transmission is desired at a desiredwavelength (in this example about 480 nm), then only certaincombinations of thin film and tint transmissions may be used.Furthermore, if about 10% reflection is desired, then only a singlecombination of thin film and tint transmissions is allowed. Theserelationships may be described as follows:

$\begin{matrix}{{{T_{tint}^{2}(\lambda)} - {{T(\lambda)}{T_{tint}(\lambda)}} - {R(\lambda)}} = 0} & (6) \\{{T_{film}(\lambda)} = \frac{T(\lambda)}{T_{tint}(\lambda)}} & (7)\end{matrix}$

The dose D experienced by melanopsin cells due to back reflected lightinto the user's eyes can be written similarly to the dose experienced bymelanopsin cells due to transmitted light shown in Equation (1)

$\begin{matrix}{D_{R - {melan}} = {\int{{L(\lambda)}{R(\lambda)}{M(\lambda)}d\;\lambda}}} & (8)\end{matrix}$where L is the light spectrum (in terms of intensity, power,photons/sec, etc.), R is the spectral back reflection, and M is thenormalized action potential response spectrum of melanopsin, ascurrently estimated from FIG. 1 as a Gaussian function centered at 480nm with a full-width at half-maximum of 52 nm. For generality, it isassumed that L=1 so as not to limit discussion to any specific lightsource, however analyses may be performed for any light source of knownspectrum.

The normalized dose by back reflected light experienced by melanopsincells may be calculated by

$\begin{matrix}{N_{R\text{-}{melan}} = \frac{D_{R\text{-}{melan}}}{D_{melan}\left( {T = 1} \right)}} & (9)\end{matrix}$

A similar dose and normalized dose can be calculated in association withthe visual response spectrum

$\begin{matrix}{D_{R\text{-}{vis}} = {\int{{L(\lambda)}{R(\lambda)}{V(\lambda)}d\;\lambda}}} & (10) \\{N_{R\text{-}{vis}} = \frac{D_{R\text{-}{vis}}}{D_{vis}\left( {T = 1} \right)}} & (11)\end{matrix}$where V represents the normalized visual response spectrum. Ideally,backreflection would be reduced so that these dose values are close tozero.

The dose of back reflected light with respect to the action potentialspectrum of the melanopsin pathway may be determined using Equation (8).The dose of back reflected light with respect to the visual spectrum maybe determined using Equation (9). The doses of back reflected light maybe used to design and manufacture an optical filter. For example, anappropriate level of tinting may be selected based on the maximumdesired dose of back reflected light, whether across the actionpotential spectrum of the melanopsin pathway, across the visualspectrum, or both. Reduction of the dose and normalized dose of backreflected light experienced by melanopsin cells may reduce the symptomsexperienced by a photophobic user.

The following tables illustrate additional embodiments of filter designswith some possible combinations of notch and tint transmissions thatresult in specific transmissions and backside reflections at, forexample, about 480 nm. Note that, due to the notch response, thetransmission of light outside the notch will be greater than thetransmission of light within the notch, so that the amount of backreflected light will be less than occurs at the notch center. Althoughthese examples are specific to a notch centered near 480 nm, otherwavelengths may be selected as described herein.

Table 1 provides examples that maintain a fixed 10% backside reflectionat a specific wavelength (around 480 nm, for example) or range ofwavelengths, with different transmissions through the frontside. Thisvalue of backside reflection might be desirable for therapeutic lensesthat may be used in “open” style spectacle frames, for example, wherelight is allowed to strike the lenses from the top, bottom, and/orsides, thereby entering the backside of the lens and reflecting into theeyes of the user from the front-side thin-film coating. Other amounts ofbackside reflection may be desirable for other style spectacle frames(such as sport glasses, wraparound sunglasses, or other styles offrames).

TABLE 1 transmission T back refl R T_(tint) T_(film) 0.50 0.10 0.65 0.770.45 0.10 0.61 0.73 0.40 0.10 0.57 0.70 0.35 0.10 0.54 0.65 0.30 0.100.50 0.60 0.25 0.10 0.47 0.54 0.20 0.10 0.43 0.46 0.15 0.10 0.40 0.380.10 0.10 0.37 0.27

Table 2 provides further embodiments, but with greater backsidereflection allowed. These designs may be more appropriate for “wrap”style spectacle or sport frames, which prevent light from entering theeyes except for that light which passes through the front-side of thelenses.

TABLE 2 transmission T back refl R T_(tint) T_(film) 0.50 0.35 0.89 0.560.45 0.35 0.86 0.52 0.40 0.35 0.82 0.49 0.35 0.35 0.79 0.44 0.30 0.350.76 0.39 0.25 0.35 0.73 0.34 0.20 0.35 0.70 0.29 0.15 0.35 0.67 0.220.10 0.35 0.64 0.16

Other embodiments of a filter may include fixing the notch transmissionand adjusting the tint transmission to provide a given backsidereflection value. Examples of these embodiments are shown in Table 3below.

TABLE 3 transmission T_(film) back refl R T_(tint) trans T 0.35 0.050.28 0.10 0.35 0.10 0.39 0.14 0.35 0.15 0.48 0.17 0.35 0.20 0.55 0.190.35 0.25 0.62 0.22 0.35 0.30 0.68 0.24 0.35 0.37 0.75 0.26 0.25 0.450.77 0.19 0.15 0.50 0.77 0.12

The R values described herein may be used to determine the maximumamount of back reflected light. For example, an R value of about 0.10could be used as a desired amount of back reflected light weightedacross the action potential spectrum of the melanopsin pathway, thevisual spectrum, or both. As the R values are based on a desiredwavelength to attenuate, other wavelengths of light may be attenuatedbased on a filter designed to achieve an R value equal to or less thanvalues according to the tables above. For example, for a wavelength ofabout 480 nm with an R value of about 0.10, the R value for a wavelengthof about 470 nm or 490 nm may be less than 0.10, such as about 0.09. Rvalues will generally decrease at wavelengths away from the desirednotch center wavelength. For clarity, though the tables herein list theR value as a decimal value, these values may also be expressed aspercentages.

These examples are not intended to limit the combinations appropriatefor the present disclosure and are provided only to demonstrate some ofthe possible combinations that may be appropriate for therapeuticeffects. Any number of other combinations are envisioned and may beappropriate for different levels of user light sensitivity, fordifferent diseases, for different applications, and for different typesof tints (e.g. gray, FL-41, etc.), and different frame styles.

Manufacturing considerations may also be taken into account whenperforming filter design. For example, material deposition is typicallyaccomplished using sputtering, evaporation, or chemical vapor depositiontechniques. Deposition conditions may be optimized to minimize stress ofthe thin film materials. Oftentimes high temperature thermal annealingmay be performed post-deposition to relax stress in the depositedmaterials, but annealing often cannot be applied to plastic lenses.Spectacle lenses represent curved substrates, so that achieving constantfilm thickness during deposition may be a challenge. To produce constantfilm thicknesses, modification of the target-source geometry in thedeposition system may be used. For plastic lenses, low temperaturedeposition may be used, but may be optimized to produce low stressfilms.

The following working examples describe tested optical filter designsand their results. Test notch coatings were produced on polycarbonate orCR-39 plano lenses with scratch resistant coatings. A thin layer of Crwas deposited on to the substrate to act as an adhesion layer for thethin film stack. The transmission spectrum through an example coatedlens is shown in FIG. 18A. The center of the notch is at about 482.9 nmwith width of about 55.5 nm, with minimum transmittance of about 24.5%.This embodiment of a filter blocks about 58% of the melanopsin actionpotential spectrum and blocks about 23% across the visible spectrum,with an FOM value of about 2.6. In contrast, FIG. 18B depicts atransmission spectrum of a coated lens with a 620 nm notch filter.

In a preliminary clinical trial, migraine sufferers were recruited towear spectacles with the therapeutic notch coating of FIG. 18A.Participants wore therapeutic lenses for 2 weeks. For inclusion in thetrial, all participants reported chronic daily headache, defined as morethan 15 days with headache per month. A validated questionnaire, HIT6,was used to assess the effects of headaches on the participants' dailylives, both before and after wearing the therapeutic lenses. Atabulation of the HIT6 scores is shown in the following table. Anaverage of about 6.6% improvement was obtained, consistent with asignificant improvement in quality of life for the participants.

Participant HIT6 before HIT6 after Improvement #1 61 57 6.6% #2 76 68 11% #3 65 62 4.6% #4 55 48  13% #5 70 68 2.9% #6 69 65 5.8% #7 61 584.9% #8 63 60 4.8% #9 69 60  13% #10 68 67 1.5% #11 68 65 4.4%

In another working example, thin film notch coatings have been appliedto FL-41 tinted lenses. The transmission and backside reflection spectraare shown in FIGS. 19 and 20. Different levels of FL-41 tint wereapplied to tintable scratch resistant layers (also called hard coatings)on the polycarbonate or CR-39 lenses. The multi-layer notch filter wasthen applied to the front side of each lens, with a conventionalanti-reflection coating applied to the backside of each lens. As can beseen from FIGS. 19 and 20, the FL-41 tint dramatically decreased thebackside reflection. However, in the transmission, the notch response isred-shifted due to the slope of the FL-41 tint near 480 nm. This shiftmay be compensated for by starting with a slightly blue-shifted notchdesign.

The following table lists the blocking levels across the melanopsin andvisual response spectrum and the FOM values for each tint level. Similarresults can be expected by utilizing other tints, such as gray tintssuch as “sun gray” from BPI.

FL-41 tint level Melanopsin blocking Visual blocking FOM  0% 67.5% 28.8%2.3 15% 71.3% 36.9% 1.9 35% 78.9% 53.7% 1.5 50% 88.0% 70.4% 1.3

The coatings described here can also be integrated with othertechnologies. For example, filter coatings can be applied to tintedlenses, photochromic materials may be incorporated, techniques forpolarization can be included, other technologies may be integrated, orcombinations thereof. In addition, combinations of filter technologiesmay be used, such as applying a nanoparticle filter coating on top of amulti-layer thin-film coating. Active materials, such as electro-opticmaterials, including electro-optic polymers, liquid crystals, or otherelectro-optic materials, piezoelectric materials, includingpiezoceramics such as PZT, or other piezoelectric materials may be used.

FIG. 21 illustrates an exemplary embodiment of a method 2100 ofmanufacturing an optical filter for reducing the frequency and/orseverity of photophobic responses. The method 2100 may be used to designat least one embodiment of a filter described herein. The method 2100may include determining the appropriate light spectrum, as illustratedby act 2102. Determining the appropriate light spectrum may includeconsideration of specific lighting conditions, such as takingspectrophotometric measurements, in conditions such as indoorfluorescent lighting and/or computer screens in an office, shopping, orhome environment, or outdoor lighting such as sunlight experienced dueto normal outdoor activities or sporting activities. The light dose tobe experienced by melanopsin cells may be determined (using, forexample, Equation 1), as illustrated by act 2104. The light dose to beexperienced across the visual response spectrum may be determined(using, for example, Equation 2), as illustrated by act 2106. An opticalfilter may be designed and manufactured using the first light dose andthe second light dose, as illustrated by act 2108. The first light doseand the second light dose may be used to determine a figure of merit(FOM) as described herein. In other embodiments, the dose across thevisual response spectrum may be considered for a portion or portions ofthe visible spectrum. For example, more or less than the entire visualresponse spectrum may be used.

FIG. 22 illustrates an exemplary embodiment of a method 2200 forreducing the frequency and/or severity of photophobic responses or formodulating circadian cycles. The method 2200 may be used in conjunctionwith at least one embodiment of a filter described herein. The method2200 may include receiving an amount of light, as illustrated by act2202. The light received may include direct or indirect light from oneor more light sources. Less than a first amount of light weighted acrossthe action potential spectrum of the melanopsin cells may betransmitted, as illustrated by act 2204. A second amount of lightweighted across the visual light spectrum may be transmitted, asillustrated by act 2206. An optical filter may be manufactured using thefirst light dose and the second light dose, as illustrated by act 2208.The first light dose and the second light dose may be used to determinea figure of merit (FOM) as described herein. In other embodiments, thedose across the visual response spectrum may be reduced or separated.For example, more or less than the entire visual response spectrum maybe used.

In addition to regulating the exposure of melanopsin ganglion cells tolight near 480 nm, it has been demonstrated through clinical testingthat attenuation of light at a wavelength of about 620 nm may also yieldimprovements in alleviating symptoms associated with light sensitivity.Although light wavelengths at about 620 nm are not believed to act onthe melanopsin ganglion cells, attenuation of light at about 620 nm hasbeen demonstrated to reduce symptoms of light sensitivity in somepeople, such as pain or discomfort in response to light, and thefrequency and/or severity of migraine and other headaches, and may alsoprove effective for some in the treatment of blepharospasm,post-concussion/TBI syndrome, sleep disorders, epilepsy.

In one embodiment, improvements may be realized by attenuating lightbetween about 580 nm and about 650 nm. In another embodiment,improvements may be realized by attenuating light between about 600 nmand about 640 nm. In yet another embodiment, improvements may berealized by attenuating light using a filter substantially centered at awavelength of 620 nm with a full-width at half-maximum of about 55 nm.

Additionally, a filter may attenuate light wavelengths in multipleranges. For example, an embodiment of a filter may attenuate light atabout 620 nm in addition to attenuating light at about 480 nm. Inanother embodiment, a filter may preferentially attenuate lightwavelengths from about 450 nm to about 510 nm and from about 580 nm toabout 640 nm. In yet another embodiment, a filter may attenuate lightbetween about 470 and about 490 and between about 610 nm and about 630nm.

An optical filter may be made in accordance with the previouslydescribed processes and using the previously described materials. Forexample, a 620 nm optical filter may comprise a high pass filter, a lowpass filter, or an optical notch filter. The optical notch filter maycomprise a plurality of layers of dielectric materials, nanoparticlesdistributed on or embedded in a host medium, or a combination thereof.In addition, any of the aforementioned combinations may be used inconjunction with a dye incorporated in a substrate. By way of example,producing short pass or notch filters may include using alternatinglayers of high and low refractive index materials. Example low indexdielectric materials include MgF₂ and SiO₂. Example high index materialsinclude metal oxides such as TiO₂, Ti₃O₅, ZrO₂, and Ta₂O₅, and Si₃N₄.Numerous other suitable materials can be used, including polymer layers.

Similarly to the embodiments that are intended to attenuate wavelengthsabsorbed by the melanopsin ganglion cells and were described previously,an optical filter designed to attenuate wavelengths at about 620 nm maybe manufactured according to a similar FOM. The light dose D received atabout 620 nm can be written

$\begin{matrix}{D_{{rec},620} = {\int{{L(\lambda)}{T(\lambda)}{R_{620}(\lambda)}d\;\lambda}}} & (12)\end{matrix}$where L is the light spectrum (in terms of intensity, power,photons/sec, etc.), T is the spectral

a filter lying between the light source and the eye, and R₆₂₀ is theidealized response spectrum at about 620 nm, which may be estimated as aGaussian function centered at 620 nm with a full-width at half-maximumof 50, 55 or 60 nm, although other values are anticipated and may provetherapeutic. For generality, it is assumed that L=1 so as not to limitdiscussion to any specific light source, however analyses may beperformed for any light source of known spectrum.

A similar dose can be calculated in association with the visual responsespectrum

$\begin{matrix}{D_{vis} = {\int{{L(\lambda)}{T(\lambda)}{V(\lambda)}d\;\lambda}}} & (13)\end{matrix}$where V represents the normalized visual response spectrum.

The effect of an optical filter, such as a nanoparticle notch filter, isto reduce the dose, as described by taking the ratio of dose calculatedwith the filter to dose without the filter, for example

$N_{{rec},620} = \frac{D_{{rec},620}}{D_{{rec},620}\left( {T = 1} \right)}$

The “attenuation” of the dose may be written as, for example,

$A_{{rec},620} = {{1 - N_{{rec},620}} = {1 - \frac{D_{{rec},620}}{D_{{rec},620}\left( {T = 1} \right)}}}$

An FOM can also be defined which compares the blocking of the light atabout 620 nm to the blocking of the visual response spectrum

$\begin{matrix}{{FOM} = \frac{1 - \frac{D_{{rec},620}}{D_{{rec},620}\left( {T = 1} \right)}}{1 - \frac{D_{vis}}{D_{vis}\left( {T = 1} \right)}}} & (14)\end{matrix}$which represents the ratio of the attenuation of light at about 620 nmto the attenuation of light across the visible spectrum, where a valueof FOM>1 may be desirable. Using the method described above to estimatethe visual response at about 620 nm, the comparison becomes morestringent as a smaller full width half maximum value is used. Forexample, when R(λ), the Gaussian distribution used in the estimate, hasa full width half maximum of 50 nm describes a more specific opticalfilter than that when the estimate includes an R(λ) having a 60 nm fullwidth half maximum.

The optical filter may comprise a multilayer dielectric film similar tothat described for the attenuation of light to which melanopsin cellsare sensitive, or the optical filter may comprise a nanoparticle-basedoptical filter, a color filter, a tint, a resonant guided-mode filter, arugate filter, or any combination thereof. A nanoparticle-based opticalnotch filter may comprise nanoparticles distributed on the surface of orembedded in a host medium. Such a filter may therefore be used in asubstantially transparent host medium, such as the lens material ofeyeglasses or simply applied to a surface thereof. For example, thefilter may be disposed on the surface of eyeglass lenses to attenuatelight approaching a user's eyes. In another application, the filter maybe disposed on the source of light directly, for example, over anelectronic display such as computer screen or on a lighting source suchas a light bulb or anuation of light by nanoparticle-based notch filtermay be adjusted via the shape of the nanoparticles, the amount ordensity of nanoparticles on or embedded in the host medium, thecomposition of the nanoparticles, the size of the nanoparticles, and theindex of refraction of the host medium. The attenuation spectrum of ananoparticle-based optical notch filter may therefore be tuned to aparticular curve by selecting materials and distributions that centerthe curve at a desired wavelength and a produce an attenuation curvewith a maximum attenuation at a desired wavelength value and anappropriate shape and full width half maximum.

For example, increasing the index of refraction of the host medium ofthe nanoparticles may shift the attenuation spectrum toward longerwavelengths, as may utilizing larger particle sizes, including solid andcore-shell particles, and/or utilizing other metals. The attenuationspectrum changes because the attenuation is due, at least in part, tolocalized surface plasmonic resonance (LSPR). The scattering due to theLSPR is proportional to the relative index of the refraction of the hostmedium. Therefore, when the index of refraction of the host mediumincrease, not only does the attenuation spectrum redshift, but theamount of scattering, and hence the amount of attenuation of light,increases as well.

The position and amount of scattering due to the LSPR is at leastpartially dependent on the relative index of refraction between theparticles and the host medium. The relative index of refraction canalso, therefore, be altered by changing the nanoparticle composition.The nanoparticles may be solid, consisting of a single material, or acore-shell composition having a core of a first material and a shell ofa second material. In either case, the materials may be a singleelement, a compound, or an alloy. As described earlier, thenanoparticles may include metallic nanoparticles (e.g. Al, Ag, Au, Cu,Ni, Pt), dielectric nanoparticles (e.g. TiO₂, Ta₂O₅, etc.),semiconductor nanoparticles or quantum dots (e.g. Si, GaAs, GaN, CdSe,CdS, etc.), magnetic nanoparticles, core-shell particles consisting ofone material in the core and another serving as a shell, othernanoparticles, or combinations thereof. By way of example, increasingthe proportion of Ag in an Ag/Al alloy solid nanoparticle may redshiftand increase the amplitude of the attenuation curve for thatnanoparticle.

In addition, the nanoparticles used may have cross-sections including acircle, an ellipse, a rectangle, a hexagon, an octagon, or otherpolygon. Spherical particles have the most focused spectrum because theyhave a single, narrow primary peak that allows for optimization usingsize and composition changes. However, it is possible to utilize acombination of particles of other shapes in order to develop a desiredfilter spectrum. One may broaden the extinction spectrum of a 40 nmspherical nanoparticle filter by simply introducing, for example, cubicnanoparticles or octahedral nanoparticles of an equivalent size.

In contrast, the attenuation curve of a core-shell nanoparticle may betuned by altering the relative thicknesses of the core and shell. By wayof example, decreasing the thickness of an Ag shell relative to the sizeof a SiO₂ core may reduce the full width half maximum of the attenuationspectrum. Shapes of these particles may be spherical, ellipsoidal,otherwise shaped, or combinations thereof. The shape of the particlesmay also affect the shape and amplitude of the attenuation curve. In anembodiment, the optical filter comprises spherical core-shellnanoparticles. In a further embodiment, the spherical core-shellnanoparticles have an Ag shell and a Si core. In a yet furtherembodiment, the spherical Ag/Si core-shell nanoparticles have an Agshell with a radial thickness of 45 nm and a Si core with a radius of 15nm.

FIG. 23 depicts a nanoparticle-based optical filter used in conjunctionwith a multilayer thin film filter to form a composite filter 2300. Afirst filter may attenuate light in a first range of wavelengths,thereby substantially reducing or removing those wavelengths in thelight spectrum entering the second filter. In the depicted embodiment,ambient light 2302 may enter a filter comprising nanoparticles 2304 thatmay be disposed on or embedded in a host medium 2306 that is disposed ona surface of the thin film filter 2308. Alternatively or in addition, athin film filter and a nanoparticle-based filter may be disposed onopposing surfaces of a substrate, such as the lenses of eyeglasses. Inanother embodiment, nanoparticles may be embedded within a thin filmfilter, and one or more layers of the thin film may be the host mediumfor the nanoparticle-based filter. The ambient light 2302 that entershost medium 2306 with nanoparticles 2304 embedded therein may besunlight. The attenuated light 2310 that enters the thin film filter2308 may have a reduced amount of light in the range attenuated by thenanoparticles 2304. The filtered light 2312 that exits the compositefilter 2300 may be attenuated in two ranges of wavelengths. Similarly, a“double notch” filter may be implemented entirely through the use ofmulti-layer thin film coatings.

FIG. 24 illustrates an embodiment of a method 2400 of manufacturing acomposite optical filter for reducing the frequency and/or severity ofphotophobic responses. The method 2400 may be used to design at leastone embodiment of a composite filter described herein. The method 2400may include determining the appropriate light spectrum, as illustratedby act 2402. Determining the appropriate light spectrum may includeconsideration of specific lighting conditions, such as takingspectrophotometric measurements, in conditions such as indoorfluorescent lighting and/or computer screens in an office, shopping, orhome environment, or outdoor lighting such as sunlight experienced dueto normal outdoor activities or sporting activities.

A first light dose to be experienced by the subject may be determined(using, for example, Equation 1), as illustrated by act 2404. A secondlight dose to be experienced by a human eye at a wavelength at about 620nm may be estimated (using, for example, Equation 12), as illustrated byact 2406. A third light dose to be experienced across the visualresponse spectrum may be determined (using, for example, Equation 13),as illustrated by act 2408. An optical filter may be designed andmanufactured using the first light dose, the second light dose, and thethird light dose, as illustrated by act 2410. The first light dose andthe second light dose may each be used with the third light dose todetermine a figure of merit (FOM) for each as described herein. In otherembodiments, the dose across the visual response spectrum may beconsidered for a portion or portions of the visible spectrum. Forexample, more or less than the entire visual response spectrum may beused.

FIG. 25 illustrates an embodiment of a method 2500 using a compositefilter for reducing the frequency and/or severity of photophobicresponses or for modulating circadian cycles. The method 2500 may beused in conjunction with at least one embodiment of a composite filterdescribed herein. The method 2500 may include receiving an amount oflight, as illustrated by act 2502. The light received may include director indirect light from one or more light sources. A first amount oflight that is attenuated preferentially across the action potentialspectrum of the melanopsin cells may be transmitted, as illustrated byact 2504. A second amount of light that is attenuated preferentially ina wavelength range at about 620 nm may be transmitted, as illustrated byact 2506. A third amount of light may then be transmitted to a humaneye, as illustrated by act 2508. In other embodiments, the dose acrossthe visual response spectrum may be reduced or separated. For example,more or less than the entire visual response spectrum may be used.

Efficacy testing has been conducted verifying the benefits ofattenuating light near about 480 nm and 620 nm. Preliminary testingincluded a prospective, double-masked, crossover clinical study todetermine the efficacy of customized, thin film spectacle coatings inthe treatment of chronic migraine. Subjects wore two differentspectacles during the trial: one coating was a notch filter at 480 nm.The other coating was a notch filter at 620 nm. Typical transmissionspectra of gray tinted lenses with the different coatings used in thisstudy are shown in FIGS. 23A and 23B. The 480 nm notch filter shownblocks about 68% of light absorption by melanopsin, and blocks 42% ofvisible light. The 620 nm notch filter shown blocks about 66% of lightabsorption centered at 620 nm with a ˜55 nm width and blocks about 42%of visible light. The 480 nm filters used in the study had averageblocking around 480 nm of 68±6% and average visible blocking of 44±4%.The 620 nm filters used in the study had average blocking around 620 nmof 67±2% and average visible blocking of 43±4%. Neither the subjects northe clinical coordinators were informed which lenses had a 480 nm notchfilter and which had a 620 nm notch filter. Subjects in the study had tocarry a diagnosis of chronic migraine, meaning that they have at least15 headache-days per month. Individuals with at least 15 headache-daysper month are considered the most severely affected migraine patients.

To assess the efficacy of the intervention, the 6-question “HeadacheImpact Test” (“HIT-6”) was chosen as the primary outcome measure. TheHIT-6 is a 6-question instrument that has been designed and validated toassess the impact of headaches on a person's life. The score is acontinuous variable that ranges from a minimum of 36 to a maximum of 78.A score less than 50 indicates that headaches are having little impacton one's life, a score of 50-55 indicates “some impact,” a score of56-59 indicates “substantial impact,” and a score over 60 is consistentwith a “very severe impact” of headaches.

Subjects first completed a four-week “pre-wash” during which no studylenses were worn. This period helped establish base-line characteristicsof their headaches. Subjects were randomized to wear either one or theother lens first, utilizing block randomization. They were instructed towear the spectacles full-time for two weeks. They then had a two-week“washout” period during which no study lenses were worn. The subjectsthen wore the other lens for another two-week period. Finally, subjectsunderwent a final “post-wash” period during which no study lenses wereworn to establish an exit “finish line” for headache characteristics.

There is a considerable amount of variability in the frequency andseverity of headaches. In some cases, this variability may occur even inthe same patient. The “pre-wash” and “post-wash” periods were added todue to the variability. These additional periods, during which no studylenses are worn, minimized the effect of “baseline drift” in the studysubjects.

The HIT-6 questionnaire was administered before the study and after eachof the period of the study, resulting in six completed questionnairesfor each subject. The study included forty-eight participants initially,and thirty-seven of the participants completed the course of the study.Of the thirty-seven subjects who completed the study, the baseline HIT-6score was 64.5. Thirty-three of the thirty-seven subjects (89%) hadbaseline HIT-6 scores greater than or equal to 60. According to theHIT-6 interpretation, these thirty-three subjects have headaches thatare having a “very severe impact” on their lives. Both the 480 nm and620 nm filter lenses displayed a statistically significant reduction inHIT-6 values.

Of the thirty-seven participants that completed the study, nine subjectswere able to move out of the “very severe impact” HIT-6 category whilewearing the 480 nm lenses; five subjects were able to move out of thiscategory wearing the 620 nm lenses and five subjects were able to moveout of this category wearing either of the lenses. Ten subjectsexperienced at least a 6-point improvement in HIT-6 when wearing the 480nm lenses, ten subjects experienced at least a 6-point improvement inHIT-6 when wearing the 620 nm lenses and three subjects experienced atleast a 6-point improvement in HIT-6 when wearing either of the lenses.This analysis indicates that wearing either the 480 nm or 620 nmspectacle lenses resulted in statistically significant reductions inHIT-6. However, there was no significant difference comparing the effectof the 480 nm lenses to the 620 nm lenses (p=0.195) . . . .

Secondary outcomes gleaned from the diaries, including percent days withsevere headache, percent days where activity had to be changed orsubject had to go to bed, and percent days requiring an abortivemedication, behaved similar to the primary outcome for either the 480 nmor 620 nm spectacle lenses: Subjects experienced significant reductionsin these parameters wearing either the 480 nm or 620 nm lenses. Therewas no significant difference comparing the effect of the 480 nm lensesto the 620 nm lens for any of these three outcomes.

The melanopsin of the melanopsin ganglion cells is a bistable pigment.Melanopsin may undergo an isomerization during exposure to light atcertain wavelengths. FIG. 27 is a graph 2700 schematically depicting thecyclic isomerization of a bistable pigment as the pigment is exposed todifferent wavelengths of light. The bistable pigment may have firstisoform that exhibits a first absorption spectrum 2702. The firstabsorption spectrum absorbs a first wavelength 2704. The first isoformof the bistable pigment may react with the first wavelength 2704. Thefirst wavelength 2704 may isomerize the bistable pigment and may triggera phototransduction cascade in an associated cell or membrane. In anembodiment, the bistable pigment may be melanopsin and exposure to afirst wavelength 2704 may trigger a phototransduction cascade in themelanopsin ganglion cell. Exposure to the first wavelength may cause thebistable pigment to isomerize from the first isoform to a secondisoform. The first isoform may be an active 11-cis isoform ofmelanopsin. The second isoform may be an inactive metamelanopsinisoform. The isomerization of the active 11-cis isoform may lead to thephototransduction cascade.

The second isoform may exhibit a second absorption spectrum 2706. Thesecond absorption spectrum 2706 may absorb a second wavelength 2708. Thesecond isoform of the bistable pigment may react with the secondwavelength 2708. In an embodiment, the first isoform may be an activeisoform of the bistable pigment and the second isoform may be aninactive isoform of the bistable pigment. In another embodiment, thefirst isoform may be an inactive isoform of the bistable pigment and thesecond isoform may be an active isoform of the bistable pigment. In yetanother embodiment, the first isoform may be an active isoform ofmelanopsin and the second isoform may be an inactive isoform ofmelanopsin.

FIG. 28 depicts a graph 2800 of an active absorption spectrum 2802 andan inactive absorption spectrum 2804 for melanopsin. The activeabsorption spectrum 2802 and inactive absorption spectrum 2804 eachcorrespond to an active isoform of melanopsin and an inactive isoform ofmelanopsin, respectively. “Active” and “inactive” should be understoodas referring to the physiological activity of the pigment and thepigment's ability to contribute to photophobic responses in anindividual rather than the pigment's ability to absorb light. The activeabsorption spectrum 2802 may have a maximum at approximately 484 nm. Theinactive absorption spectrum 2804 may have a maximum at approximately587 nm.

The inactive isoform of melanopsin may absorb wavelengths of lightaccording to the inactive absorption spectrum 2804. The light absorbedby the inactive isoform of melanopsin may contribute to the conversionof the inactive isoform to the active form of melanopsin. The activeform of melanopsin may contribute to a photophobic response of anindividual. In at least one embodiment, an attenuation of light absorbedby the inactive isoform may disrupt the isomerization of melanopsin andreduce symptoms of light sensitivity in some people, such as pain ordiscomfort in response to light, and the frequency and/or severity ofmigraine and other headaches, and may also prove effective for some inthe treatment of blepharospasm, post-concussion/TBI syndrome, sleepdisorders, epilepsy.

In addition to regulating the exposure of melanopsin ganglion cells tolight near 480 nm and/or 620 nm, the attenuation of light at theabsorption maximum of the inactive absorption spectrum for the inactiveisoform of melanopsin may also yield improvements in alleviatingsymptoms associated with light sensitivity. For example, an opticalfilter centered at a wavelength of about 590 nm may attenuate the lightabsorbed by the inactive isoform of melanopsin.

In one embodiment, improvements may be realized by attenuating lightbetween about 560 nm and about 620 nm. In another embodiment,improvements may be realized by attenuating light between about 570 nmand about 610 nm. In yet another embodiment, improvements may berealized by attenuating light using a filter substantially centered at awavelength of 590 nm with a full-width at half-maximum of about 50 nm.

Additionally, a filter may attenuate light wavelengths in multipleranges. For example, an embodiment of a filter may attenuate lightabsorbed by the inactive isoform of melanopsin and light absorbed by theactive isoform of melanopsin. In an embodiment, a filter may attenuatelight at about 590 nm in addition to attenuating light at about 480 nm.In another embodiment, a filter may preferentially attenuate lightwavelengths from about 450 nm to about 510 nm and from about 560 nm toabout 620 nm. In yet another embodiment, a filter may attenuate lightbetween about 470 and about 490 and between about 580 nm and about 600nm.

Similarly to the previously described 480 nm filter and the 620 nmfilter, an optical filter capable of attenuating 590 nm light maycomprise a high pass filter, a low pass filter, an optical notch filter,or combinations thereof. The optical notch filter may comprise aplurality of layers of dielectric materials, nanoparticles distributedon or embedded in a host medium, or a combination thereof. In addition,any of the aforementioned combinations may be used in conjunction with adye incorporated in a substrate. By way of example, producing short passor notch filters may include using alternating layers of high and lowrefractive index materials. Example low index dielectric materialsinclude MgF₂ and SiO₂. Example high index materials include metal oxidessuch as TiO₂, Ti₃O₅, ZrO₂, and Ta₂O₅, and Si₃N₄. Numerous other suitablematerials can be used, including polymer layers.

Similarly to the embodiments that are intended to attenuate wavelengthsabsorbed by the active isoform of melanopsin and were describedpreviously, an optical filter designed to attenuate wavelengths at about590 nm may be manufactured according to a similar FOM. The light dose Dreceived at about 590 nm can be written

$\begin{matrix}{D_{{rec},590} = {\int{{L(\lambda)}{T(\lambda)}{R_{590}(\lambda)}d\;\lambda}}} & (15)\end{matrix}$where L is the light spectrum (in terms of intensity, power,photons/sec, etc.), T is the spectral transmission of a filter lyingbetween the light source and the eye, and R₅₉₀ is the idealized responsespectrum at about 590 nm, which may be estimated as a Gaussian functioncentered at 590 nm with a full-width at half-maximum of 50, 55, or 60nm, although other values are anticipated and may prove therapeutic. Forgenerality, it is assumed that L=1 so as not to limit discussion to anyspecific light source, however analyses may be performed for any lightsource of known spectrum.

A similar dose can be calculated in association with the visual responsespectrum

$\begin{matrix}{D_{vis}{\int{{L(\lambda)}{T(\lambda)}{V(\lambda)}d\;\lambda}}} & (16)\end{matrix}$where V represents the normalized visual response spectrum.

The effect of an optical filter, such as a nanoparticle notch filter, isto reduce the dose, as described by taking the ratio of dose calculatedwith the filter to dose without the filter, for example

$N_{{rec},590} = \frac{D_{{rec},590}}{D_{{rec},59}\left( {T = 1} \right)}$

The “attenuation” of the dose may be written as, for example,

$A_{{rec},590} = {{1 - N_{{rec},590}} = {1 - \frac{D_{{rec},590}}{D_{{rec},590}\left( {T = 1} \right)}}}$

An FOM can also be defined which compares the blocking of the light atabout 590 nm to the blocking of the visual response spectrum

$\begin{matrix}{{FOM} = \frac{1 - \frac{D_{{rec},590}}{D_{{rec},590}\left( {T = 1} \right)}}{1 - \frac{D_{vis}}{D_{vis}\left( {T = 1} \right)}}} & (17)\end{matrix}$which represents the ratio of the attenuation of light at about 590 nmto the attenuation of light across the visible spectrum, where a valueof FOM>1 may be desirable. Using the method described above to estimatethe visual response at about 590 nm, the comparison becomes morestringent as a smaller full width half maximum value is used. Forexample, when R(λ), the Gaussian distribution used in the estimate, hasa full width half maximum of 50 nm describes a more specific opticalfilter than that when the estimate includes an R(λ) having a 60 nm fullwidth half maximum.

FIG. 29 depicts a method 2900 for reducing symptoms associated withphotophobic responses. The method 2900 includes receiving 2902 light andattenuating a first wavelength 2904 and, optionally, a second wavelength2906. The attenuation of the first wavelength may then disrupt thebistable pigment cycle 2908 described in relation to FIG. 27. In anembodiment, the first wavelength may be determined by a maximum of anactive absorption spectrum or an inactive absorption spectrum of abistable pigment. In another embodiment, the first wavelength may bedetermined by the maximum of the active absorption spectrum 2802 ofmelanopsin or maximum of the inactive absorption spectrum 2804 describedin relation to FIG. 28. In yet another embodiment, the first wavelengthmay be 480 nm. In a further embodiment, the first wavelength may be 590nm.

Attenuating a wavelength should be understood to mean preferentiallyattenuating the wavelength or a range including the wavelength ascompared to other portions of the visible spectrum. For example,attenuating a 590 nm wavelength may include transmitting less light ator about the 590 nm wavelength than other light in the visible spectrum.In another example, attenuating a 590 nm wavelength may include blockingsubstantially all light at or about the 590 nm wavelength andtransmitting other light in the visible spectrum.

Attenuating the second wavelength 2906 may include attenuating a portionof a second wavelength different from the first wavelength attenuated.In an embodiment, the second wavelength may be determined by a maximumof an active absorption spectrum or an inactive absorption spectrum of abistable pigment. In another embodiment, the first wavelength may bedetermined by the maximum of the active absorption spectrum 2802 ofmelanopsin or maximum of the inactive absorption spectrum 2804 ofmelanopsin described in relation to FIG. 28. In yet another embodiment,the first wavelength may be 480 nm. In a further embodiment, the firstwavelength may be 590 nm.

Attenuating a first wavelength 2904 and, optionally, attenuating asecond wavelength 2906 may disrupt a bistable pigment cycle. Attenuatinga first wavelength 2904 may inhibit the isomerization of the bistablepigment from a first isoform to a second isoform. The first isoform maybe an active isoform or an inactive isoform. Attenuating a secondwavelength 2906 may inhibit the isomerization of the bistable pigmentfrom the second isoform back to the first isoform.

An optical filter capable of attenuating light at or about a 590 nmwavelength may be manufactured and/or tuned by any of the aforementionedprocesses such that a low pass filter, a high pass filter, or an opticalnotch filter preferentially attenuates 590 nm light. The filter mayinclude dielectric multi-layers, embedded nanoparticle coatings, a colorfilter, tint, resonant guided-mode filter, a rugate filter, and anycombination thereof. The filter may also include embedded nanoparticlecoatings such as metallic nanoparticles, dielectric nanoparticles,semiconductor nanoparticles, quantum dots, magnetic nanoparticles, orcore-shell particles having a core material in a core and a shellmaterial serving as a shell.

Because the optical filters of the present disclosure filter out certaincolors of the visible spectrum, there may be the appearance ofcoloration when viewing through the filters. A standard way ofquantifying this coloration is using the CIE chromaticity diagram,typically referring to the 1931 Standard Observer, but other versions ofthe CIE color space can be used (such as the 1964 10° chromaticitycoordinates, or coordinates based upon Stiles & Burch data, etc., whichproduce substantially similar results), in which two chromaticitycoordinates ‘x’ and ‘y’ map to human color perception. There exists apoint on the CIE chromaticity diagram, called the achromatic point (inwhich x=y=⅓) in which the perceived color is white (or gray, dependingupon the transmitted brightness, or luminance, level Y). Ideally, anoptical filter for viewing would have chromaticity coordinates x=y=⅓.

Calculation of the chromaticity coordinates is accomplished viacolor-matching functions (CMF), which are based upon physiologicalresponse to different wavelengths of light. Again, CMFs typically referto the 1931 2° data, but other CMFs can be used (such as the 1964 10°color matching functions, or CMFs based upon Stiles & Burch data), whichproduce substantially similar results. The following functions can serveas weighting factors for an input spectrum:

$\begin{matrix}{X = {\int{{L(\lambda)}{T(\lambda)}{\overset{\_}{X}(\lambda)}d\;\lambda}}} & (18) \\{Y = {\int{{L(\lambda)}{T(\lambda)}{\overset{\_}{Y}(\lambda)}d\;\lambda}}} & (19) \\{Z = {\int{{L(\lambda)}{T(\lambda)}{\overset{\_}{Z}(\lambda)}d\;\lambda}}} & (20)\end{matrix}$where X, Y and Z are known as the tristimulus values, L is the lightspectrum (in terms of intensity, power, photons/sec, etc), T is thespectral transmission of a filter lying between the light source and aperson's eye, and X, Y and Z are the color matching functions. The 1931CMFs are plotted in FIG. 30. L may be a standard illuminant, such as D50or D65 for daylight, or represent the spectrum of a specific artificiallight source such as incandescent (λ), fluorescent (series F), LED(series L), etc., but it can be assumed that L=1 (e.g. Illuminant E)without loss of generality, although any valid function L can be used.

The chromaticity coordinates may then be calculated from the tristimulusvalues:

$x = \frac{X}{X + Y + Z}$ $y = \frac{Y}{X + Y + Z}$ z = 1 − x − ywhere only x and y are necessary.

As an example, the FIG. 31 shows a 480 nm notch filter according to thepresent disclosure, along with the products T(λ)X(λ), T(λ)Y(λ), andT(λ)Z(λ), which represent the color matching functions as modified bythe presence of the filter. The tristimulus values for this filter areX=94.8, Y=92.4 and Z=58.4, with corresponding chromaticity coordinatesx=0.386 and y=0.376. Based upon the chromaticity diagram, this maps to ayellow color, meaning that the filter will modify normal color visionwith a yellow hue.

By adding a second notch at a wavelength near 590 nm, the chromaticitycoordinates of the filter can be adjusted towards the achromatic point,and therefore causing the filter to appear gray. One such embodiment isshown in FIG. 32, where the 480 nm and 590 nm notches are approximatedas Gaussian functions (center wavelengths 480 nm and 590 nm,respectively; full-widths at half-maxima of 31 nm and 50 nm; notchdepths of 0.625 and 0.41; and an overall 10% uniform reduction acrossthe visible spectrum to represent a light gray tint, which reduces theoverall transmittance but does not affect the chromaticity coordinates).

The 480 nm notch alone has tristimulus values X=91.8, Y=89.9, andZ=68.5, with chromaticity coordinates x=0.367 and y=0.359, again,producing a yellow hue. The addition of the 590 nm notch nearlyequalizes the tristimulus values at X=68.1, Y=68.4, and Z=68.2, withchromaticity coordinates x=0.3327 and y=0.3341, nearly achieving theachromatic condition.

Numerous other combinations are possible, based upon adjusting thewidths, depths, shapes, and positions of the two notches. For instance,since blocking light near 480 nm and 590 nm wavelengths is known toreduce light sensitivity and migraine, one filter design procedure is tofirst design a therapeutic 480 nm notch (i.e. designed to achieve acertain amount of blocking across the melanopsin action potentialspectrum R_(melan) or wavelength range, or to achieve a certain FOM, astaught by the present disclosure), then add a second notch at about 590nm in order to achieve the desired achromatic condition. Again, using asimplified Gaussian notch filter at 480 nm center of full-width athalf-maximum 52 nm and depth 0.625, a color balancing notch of 584 nmcenter, 51 nm width, and 0.57 depth could be used to achievechromaticity coordinates x=0.3332 and y=0.338.

In another embodiment, a color balancing notch at about 587 nm, width 67nm, and depth 0.47 could be used to achieve x=0.3323 and y=0.3340. Otherfilter design procedures can be envisioned, such as first designing a590 nm therapeutic notch (i.e. designed to achieve a certain amount ofblocking across the R₅₉₀ response function or wavelength range, orachieve a certain FOM, as taught by the present invention) and colorbalancing with a second notch at about 480 nm; designing notches at both480 nm and 590 nm and adjusting the widths and depths to simultaneouslyapproach the desired achromatic condition and achieve a certain amountof cumulative light blocking across both the R_(melan) and R₅₉₀ responsefunctions or a certain FOM taking blocking within and outside theseregions into account.

The terms “approximately,” “about,” “near,” and “substantially” as usedherein represent an amount close to the stated amount that stillperforms a desired function or achieves a desired result. For example,the terms “approximately,” “about,” and “substantially” may refer to anamount that is within less than 10% of, within less than 5% of, withinless than 1% of, within less than 0.1% of, and within less than 0.01% ofa stated amount.

It should be noted that, while the invention has been described inconnection with the above described embodiments, these descriptions arenot intended to limit the scope of the invention to the particular formsset forth, but on the contrary, these descriptions are intended to coversuch alternatives, modifications, and equivalents as may be includedwithin the scope of the invention. Any elements of the above-describedembodiments may be combined with any other elements of theabove-described embodiments. For example, any of the above-describedmethods of manufacture or methods of light attenuation may be combinedwith the described optical filters and associated wavelengths.Accordingly, the scope of the present invention fully encompasses otherembodiments that may become obvious to those skilled in the art and thescope of the present invention is limited only by the appended claims.

What is claimed is:
 1. An apparatus for modulating circadian cycles bycontrolling light exposure to melanopsin ganglion cells in a retinarelative to a visible spectrum range of 400 nm to 700 nm, the apparatuscomprising: an optical filter configured with: light transmissionfraction, averaged across wavelengths between 454 nm and 506 nm, lessthan an amount T_(melan); light transmission fraction, averaged acrosswavelengths within a visible spectrum less than 454 nm, with valuegreater than an amount T_(vis1); and light transmission fraction,averaged across wavelengths within a visible spectrum greater than 506nm, with value greater than an amount T_(vis2); wherein ratios includingsaid light transmission fractions are defined as figures of merit (FOM),the figures of merit being determined by:${FOM}_{1} = \frac{1 - T_{melan}}{1 - T_{{vis}_{1}}}$${FOM}_{2} = \frac{1 - T_{melan}}{1 - T_{{vis}_{2}}}$ wherein thefigures of merit of said optical filter are at least 1.6.
 2. Theapparatus of claim 1, wherein the optical filter further comprises: asubstrate; a first layer disposed on the substrate, the first layercomprising a high index material; and a second layer disposed adjacentthe first layer, the second layer comprising a low index material. 3.The apparatus of claim 1 wherein the optical filter includes dielectricmulti-layers, embedded nanoparticle coatings, resonant guided-modefilter, or a rugate filter.
 4. The apparatus of claim 1, wherein theoptical filter includes one or more of a color filter or a tint.
 5. Theapparatus of claim 1, wherein the figure of merit of said optical filteris at least 1.8.
 6. The apparatus of claim 1, wherein the figure ofmerit of said optical filter is at least 2.0.
 7. The apparatus of claim1, wherein the figure of merit of said optical filter is at least 2.5.8. The apparatus of claim 1, wherein the figure of merit of said opticalfilter is at least 3.0.
 9. An apparatus for modulating circadian cyclesby controlling light exposure of cells in a retina relative to a visiblespectrum range of 400 nm to 700 nm, the apparatus comprising: an opticalfilter configured with: light transmission fraction, averaged acrosswavelengths between 565 nm and 615 nm, less than an amount T_(rec,590);light transmission fraction, averaged across wavelengths within avisible spectrum less than 565 nm, with value greater than an amountT_(vis1); and light transmission fraction, averaged across wavelengthswithin a visible spectrum greater than 615 nm, with value greater thanan amount T_(vis2); wherein ratios including said light transmissionfractions are defined as figures of merit (FOM), the figures of meritbeing determined by:${FOM}_{1} = \frac{1 - T_{{rec},590}}{1 - T_{{vis}_{1}}}$${FOM}_{2} = \frac{1 - T_{{rec},590}}{1 - T_{{vis}_{2}}}$ wherein thefigures of merit of said optical filter are at least 1.3.
 10. Theapparatus of claim 9, wherein the optical filter is configured totransmit 45% of the light averaged across wavelengths between 565 nm and615 nm and 60% of the light averaged across wavelengths within thevisible spectrum less than 565 nm and greater than 615 nm.
 11. Theapparatus of claim 9, wherein the figure of merit of said optical filteris greater than 1.5, is greater than 1.8, is greater than 2.75, isgreater than 3, or is greater than 3.3.
 12. The apparatus of claim 9,wherein the optical filter includes dielectric multi-layers, embeddednanoparticle coatings, a color filter, tint, resonant guided-modefilter, a rugate filter, or any combination thereof.
 13. An apparatusfor modulating circadian cycles by controlling light exposure of cellsin a retina relative to a visible spectrum range of 400 nm to 700 nm,the apparatus comprising: an optical filter configured with: lighttransmission fraction, averaged across wavelengths between 154 nm and506 nm, less than an amount T_(melan); light transmission fraction,averaged across wavelengths between 565 nm and 615 nm, less than anamount T_(rec,590); light transmission fraction, averaged acrosswavelengths within a visible spectrum less than 154 nm, with valuegreater than an amount T_(vis1); light transmission fraction, averagedacross wavelengths within a visible spectrum greater than 506 nm andless than 565, with value greater than an amount T_(vis2); and lighttransmission fraction, averaged across wavelengths within a visiblespectrum greater than 615 nm, with value greater than an amountT_(vis2), wherein ratios including said light transmission fractions aredefined as figures of merit (FOM), the figures of merit being determinedby: ${FOM}_{1} = \frac{1 - T_{melan}}{1 - T_{{vis}_{1}}}$${FOM}_{2} = \frac{1 - T_{{rec},590}}{1 - T_{{vis}_{2\;}}}$ wherein thefigures of merit of said optical filter are at least 1.3.
 14. Theapparatus of claim 13, wherein the figure of merit of said opticalfilter is greater than 1.5, is greater than 1.8, is greater than 2.75,is greater than 3, or is greater than 3.3.
 15. The apparatus of claim13, wherein the optical filter includes dielectric multi-layers,embedded nanoparticle coatings, a color filter, tint, resonantguided-mode filter, a rugate filter, or any combination thereof.
 16. Atherapeutic treatment method for modulating circadian cycles bycontrolling light exposure of cells in a retina relative to a visiblespectrum range of 400 nm to 700 nm, the method comprising: determiningone or more light wavelength ranges that affect the circadian cycle of apatient, the light wavelength range being selected from a groupconsisting of 154 nm to 506 nm, 565 nm to 615 nm, 595 nm to 645 nm,providing an apparatus having an optical filter configured to transmit afirst amount of light within the determined light wavelength ranges(D_(rec)) and a second amount of light across the remaining visiblespectrum range (D_(vis)), wherein the optical filter has a figure ofmerit (FOM) defined by:${FOM} = \frac{1 - \frac{D_{rec}}{D_{rec}\left( {T = 1} \right)}}{1 - \frac{D_{vis}}{D_{vis}\left( {T = 1} \right)}}$where D_(rec)(T=1) is the light across the determined wavelength rangesin the absence of an optical filter, and D_(vis)(T=1) is the lightacross the remaining visible spectrum in the absence of an opticalfilter, wherein the figure of merit of said optical filter is at least1.3; and using the apparatus to controlling light exposure of cells in aretina.
 17. The method of claim 16, wherein providing the apparatuscomprises applying the optical filter to one or more lenses of a pair ofglasses.
 18. The method of claim 16, wherein using the apparatus tocontrol light exposure comprises wearing the apparatus on the patient.19. The method of claim 16, wherein providing the apparatus comprisesapplying the optical filter to one or more windows, computer screens, orlight bulbs.
 20. The method of claim 16, wherein the optical filter hasa figure of merit of at least 1.6.
 21. An apparatus for modulatingcircadian cycles by controlling light exposure of cells in a retinarelative to a visible spectrum range of 400 nm to 700 nm, the apparatuscomprising: an optical filter configured with: light transmissionfraction, averaged across wavelengths between 154 nm and 506 nm, lessthan an amount T_(melan); light transmission fraction, averaged acrosswavelengths between 565 nm and 615 nm, less than an amount T_(rec,590);light transmission fraction, averaged across wavelengths within avisible spectrum less than 154 nm, with value greater than an amountT_(vis1); light transmission fraction, averaged across wavelengthswithin a visible spectrum greater than 506 nm and less than 565, withvalue greater than an amount T_(vis2); and light transmission fraction,averaged across wavelengths within a visible spectrum greater than 615nm, with value greater than an amount T_(vis2), wherein ratios includingsaid light transmission fractions are defined as figures of merit (FOM),the figures of merit being determined by:${FOM}_{1} = \frac{1 - T_{melan}}{1 - T_{{vis}_{1}}}$${FOM}_{2} = \frac{1 - T_{{rec},590}}{1 - T_{{vis}_{2\;}}}$ wherein theFOM₁ is at least 1.3 and the FOM₂ is at least 1.1, and whereinchromaticity coordinates of said optical filter lie within the rangesx=0.33±0.02 and y=0.33±0.02.
 22. The apparatus of claim 21, wherein thechromaticity coordinates of said optical filter are x=0.386 and y=0.376.23. The apparatus of claim 21, wherein the chromaticity coordinates ofsaid optical filter are x=0.3327 and y=0.3341.
 24. The apparatus ofclaim 21, wherein the chromaticity coordinates of said optical filterare x=0.3332 and y=0.338.
 25. The apparatus of claim 21, wherein thechromaticity coordinates of said optical filter are x=0.3323 andy=0.3340.
 26. The apparatus of claim 21, wherein the figures of meritFOM₁ of said optical filter is at least 1.4 and the figure of merit FOM₂is at least 1.1.
 27. The apparatus of claim 21, wherein the figures ofmerit FOM₁ of said optical filter is at least 1.5 and the figure ofmerit FOM₂ is at least 1.2.
 28. The apparatus of claim 21, wherein thefigures of merit FOM₁ of said optical filter is at least 1.6 and thefigure of merit FOM₂ is at least 1.2.